The present invention relates to a novel antigen which is closely associated with metastatic behaviour of tumour cells in vitro and in vivo, as well as to antibodies recognising said antigen and uses thereof in diagnosis and treatment of malignancies.
Metastasis is a multi-stage process by which tumour cells leave the site of a primary tumour, enter blood and lymph vessels, migrate to distant parts of the body and form novel foci of tumour growth. In keeping with the apparently complex nature of metastasis, experimental data suggest that no one factor is exclusively responsible for the determination of metastatic potential. Rather, a cascade of events, each of which incrementally increases the liability of a tumour to metastasis, leads to metastasis and tumour spread. Each of the events of the metastatic cascade is not believed to play a role of identical importance in each metastatic situation. A given metastatic cell is likely to possess some less developed metastatic properties, but still possess high metastatic potential because other properties are highly pronounced.
For this reason, a reliable marker for metastatic potential is difficult to determine. There are indications, however, that the cell surface is closely involved with many aspects of the metastatic cascade. The detachment of tumour cells, migration through tissues and final attachment to form a new focus of growth are events which all involve the behaviour of the cell surface.
It is known to attempt to raise antibodies directed to antigens preferentially expressed by tumour cells which show metastatic potential. For example, Vollmers and Birchmeier, (1983) PNAS 80, 3739-3733 and 6863-6867, demonstrated that certain antibodies raised to mouse melanoma cell line surface protein were able to inhibit cell adhesion and block metastasis. The antibodies appeared to target antigens of between 40 and 50 kDa.
By raising antisera to membrane associated proteins and assessing cross-reactivity with transformed cells, we have now been able to identify novel 150 kDa cell-surface proteins which correlate extremely closely with metastatic potential both in vitro and in vivo.
According to the present invention, we provide membrane-associated polypeptides having the sequence shown in SEQ ID NOS. 2 and 9, respectively. Also provided are immunogenic determinants derived from said polypeptides and antibodies raised thereto. The polypeptides, their derived antigenic determinants and the antibodies are useful for the diagnosis and treatment of metastatic potential in tumours.